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ANGPTL2 Induces Synovial Inflammation via LILRB2
Sayuri Nishiyama1, Naoto Hirose2, Makoto Yanoshita1
1Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3, Minami-ku, Hiroshima-shi, Hiroshima Prefecture, Japan.
Angiopoietin-like protein 2 (ANGPTL2) drives inflammation in synovial cells through the LILRB2 receptor. Blocking LILRB2 reduces ANGPTL2-induced inflammatory gene expression and signaling pathways, suggesting LILRB2 as a therapeutic target for osteoarthritis.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Angiopoietin-like proteins (ANGPTLs) are implicated in tissue repair but ANGPTL2 can promote chronic inflammation.
- ANGPTL2 interacts with receptors like LILRB2, but its role in ANGPTL2-induced inflammation is not fully understood.
Purpose of the Study:
- To investigate the mechanisms of ANGPTL2-induced inflammation in human fibroblast-like synoviocytes (HFLS).
- To elucidate the role of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) in ANGPTL2-mediated inflammatory signaling.
Main Methods:
- Real-time RT-PCR was used to assess inflammation-related gene expression.
- Western blotting analyzed the phosphorylation of MAPK, NF-κB, and Akt signaling pathways.
- HFLS were treated with ANGPTL2 and an anti-LILRB2 antibody.
Main Results:
- ANGPTL2 significantly increased inflammatory gene expression in HFLS.
- Pretreatment with an anti-LILRB2 antibody attenuated ANGPTL2-induced inflammatory gene expression.
- ANGPTL2 activated ERK, p38, JNK, NF-κB, and Akt phosphorylation, which was inhibited by the anti-LILRB2 antibody.
Conclusions:
- ANGPTL2 induces inflammatory factor expression in synovial cells via LILRB2.
- LILRB2 is a key mediator of ANGPTL2-induced inflammation in HFLS.
- LILRB2 represents a potential therapeutic target for managing matrix degradation in osteoarthritis.
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